This is an Academic Research Enhancement Award proposal to study the role of sex hormones in the endotoxic shock induced by lipopolysaccharides (LPS) derived from the bacterium, V. vulnificus. The hypothesis to be tested with the proposed experiments (numbered below) is that different hormonal profiles between males and females predisposes the males to greatly enhanced sensitivity to the virulent sequelae of the V. vulnificus LPS. This postulate will be tested in Specific Aim 1, by experiment (1) testing the dose-dependent responses of male versus female rats to V. vulnificus LPS; in Specific Aim 2, experiment (2) determining whether ovariectomy (ov-x) results in enhanced sensitivity of female rats to LPS, and experiment (3) determining if testosterone further increases sensitivity of LPS-induced effects on ov-x female rats; in Specific Aim 3, experiment (4) if castrated male rats given estradiol-17beta have a decrease in responsiveness to LPS; and in Specific Aim 4, experiment (5) determining whether alteration of nitric oxide production shifts the responsiveness of the rats to V. vulnificus LPS.